-
Letters in Applied Microbiology Jun 2024The increasing resistance to polymyxins in Acinetobacter baumannii has made it even more urgent to develop new treatments. Anti-virulence compounds have been researched...
The increasing resistance to polymyxins in Acinetobacter baumannii has made it even more urgent to develop new treatments. Anti-virulence compounds have been researched as a new solution. Here, we evaluated the modification of virulence features of A. baumannii after acquiring resistance to polymyxin B. The results showed lineages attaining unstable resistance to polymyxin B, except for Ab7 (A. baumannii polymyxin B resistant lineage), which showed stable resistance without an associated fitness cost. Analysis of virulence by a murine sepsis model indicated diminished virulence in Ab7 (A. baumannii polymyxin B resistant lineage) compared with Ab0 (A. baumannii polymyxin B susceptible lineage). Similarly, downregulation of virulence genes was observed by qPCR at 1 and 3 h of growth. However, an increase in bauE, abaI, and pgAB expression was observed after 6 h of growth. Comparison analysis of Ab0, Ab7, and Pseudomonas aeruginosa suggested no biofilm formation by Ab7. In general, although a decrease in virulence was observed in Ab7 when compared to Ab0, some virulence feature that enables infection could be maintained. In light of this, virulence genes bauE, abaI, and pgAB showed a potential relevance in the maintenance of virulence in polymyxin B-resistant strains, making them promising anti-virulence targets.
PubMed: 38942450
DOI: 10.1093/lambio/ovae061 -
International Journal of Pharmaceutics Jun 2024This paper focuses on the preparation and characterization of antibacterial alginate microparticles containing silver@hydroxyapatite functionalized calcium carbonate...
This paper focuses on the preparation and characterization of antibacterial alginate microparticles containing silver@hydroxyapatite functionalized calcium carbonate composites for tissue engineering. Microparticles were prepared by cross-linking a silver@composite sodium alginate dispersion with CaCl. This method showed a very good silver efficiency loading and the presence of silver chloride nanoparticles was detected. Silver free microparticles, containing hydroxyapatite functionalized calcium carbonates and neat alginate microparticles were prepared as well. All microparticles were characterized for water absorption and for in vitro bioactivity by immersion in simulated body fluid (SBF). Finally, antimicrobial and antibiofilm activities as well as cytotoxicity were evaluated. Microparticles containing silver@composites exhibited good antimicrobial and antibiofilm activities against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans, but exerted a certain cytotoxicity against the tested cell models (fibroblasts and osteoblasts). Microparticles containing hydroxyapatite functionalized calcium carbonates were found to be always less cytotoxic, also in comparison to neat alginate microparticles, proving that the presence of the inorganic matrices exerts a protective effect on microparticle cytotoxicity.
PubMed: 38942183
DOI: 10.1016/j.ijpharm.2024.124393 -
Spectrochimica Acta. Part A, Molecular... Jun 2024The impact of microbial infections is increasing over time, and it is one of the major reasons for death in both developed and developing countries. colistin is...
The impact of microbial infections is increasing over time, and it is one of the major reasons for death in both developed and developing countries. colistin is considered as the antibiotic of last choice for infections brought by major multidrug-resistant (MDR), gram-negative bacteria such as Enterobacter species, Acinetobacter species, and Pseudomonas aeruginosa. Existing approaches to diagnose these resistant species are relatively slow and take up to 2 to 3 days. In this work, we propose a novel interdisciplinary method based on Raman spectroscopy and heavy water to identify colistin-resistant microbes. Our hypothesis is based on the fact that resistant bacteria will be metabolically active in the culture medium containing antibiotics and heavy water, and these bacteria will take up deuterium instead of hydrogen to newly synthesized lipids and proteins. This effect will generate a 'C - D' bond-specific Raman spectral marker. Successful identification of this band in the spectral profile can confirm the presence of colistin-resistant bacteria. We have validated the efficacy of this approach in identifying colistin-resistant bacteria spiked in artificial urine and have compared sensitivity at different bacterial concentrations. Overall findings suggest that heavy water can potentially serve as a suitable Raman probe for identifying metabolically active colistin-resistant bacteria via urine under clinically implementable time and can be used in clinical settings after validation.
PubMed: 38941753
DOI: 10.1016/j.saa.2024.124723 -
Current Microbiology Jun 2024Garlic (Allium sativum L.), particularly its volatile essential oil, is widely recognized for medicinal properties. We have evaluated the efficacy of Indian Garlic...
Garlic (Allium sativum L.), particularly its volatile essential oil, is widely recognized for medicinal properties. We have evaluated the efficacy of Indian Garlic Essential Oil (GEO) for antimicrobial and antibiofilm activity and its bioactive constituents. Allyl sulfur-rich compounds were identified as predominant phytochemicals in GEO, constituting 96.51% of total volatile oils, with 38% Diallyl trisulphide (DTS) as most abundant. GEO exhibited significant antibacterial activity against eleven bacteria, including three drug-resistant strains with minimum inhibitory concentrations (MICs) ranging from 78 to 1250 µg/mL. In bacterial growth kinetic assay GEO effectively inhibited growth of all tested strains at its ½ MIC. Antibiofilm activity was evident against two important human pathogens, S. aureus and P. aeruginosa. Mechanistic studies demonstrated that GEO disrupts bacterial cell membranes, leading to the release of nucleic acids, proteins, and reactive oxygen species. Additionally, GEO demonstrated potent antioxidant activity at IC 31.18 mg/mL, while its isolated constituents, Diallyl disulphide (DDS) and Diallyl trisulphide (DTS), showed effective antibacterial activity ranging from 125 to 500 µg/mL and 250-1000 µg/mL respectively. Overall, GEO displayed promising antimicrobial and antibiofilm activity against enteric bacteria, suggesting its potential application in the food industry.
Topics: Garlic; Oils, Volatile; Antioxidants; Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Staphylococcus aureus; Allyl Compounds; Phytochemicals; Sulfides; Bacteria; Pseudomonas aeruginosa; Disulfides; India; Plant Oils; Humans; Plant Extracts
PubMed: 38940852
DOI: 10.1007/s00284-024-03753-2 -
Journal of Bacteriology Jun 2024The cystic fibrosis (CF) lung environment is conducive to the colonization of bacteria as polymicrobial biofilms, which are associated with poor clinical outcomes for...
UNLABELLED
The cystic fibrosis (CF) lung environment is conducive to the colonization of bacteria as polymicrobial biofilms, which are associated with poor clinical outcomes for persons with CF (pwCF). spp. are highly prevalent in the CF airway, but its role in the CF lung microbiome is poorly understood. Some studies have shown spp. to be associated with better clinical outcomes for pwCF, while others show that high abundance of spp. is correlated with exacerbations. Our lab previously reported a polymicrobial culture system consisting of four CF-relevant pathogens that can be used to study microbial behavior in a more clinically relevant setting. Here, we use this model system to identify genetic pathways that are important for survival in the context of the polymicrobial community. We identified genes related to reactive oxygen species as differentially expressed in monoculture versus growth of this microbe in the mixed community. Genetic studies identified Dpr as important for survival in the community. We show that Dpr, a DNA-binding ferritin-like protein, and PerR, a peroxide-responsive transcriptional regulator of Dpr, are important for protecting from phenazine-mediated toxicity in co-culture with and when exposed to hydrogen peroxide, both of which mimic the CF lung environment. Characterizing such interactions in a clinically relevant model system contributes to our understanding of microbial behavior in the context of polymicrobial biofilm infections.
IMPORTANCE
spp. are recognized as a highly prevalent pathogen in cystic fibrosis (CF) airway infections. However, the role of this microbe in clinical outcomes for persons with CF is poorly understood. Here, we leverage a polymicrobial community system previously developed by our group to model CF airway infections as a tool to investigate a - interaction involving reactive oxygen species (ROS). We show that protection against ROS is required for survival in a clinically relevant polymicrobial system. Using this model system to study interspecies interactions contributes to our broader understanding of the complex role of spp. in the CF lung.
PubMed: 38940597
DOI: 10.1128/jb.00176-24 -
Journal of Global Health Jun 2024Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that...
Analysis of clinical characteristics, prognosis and influencing factors in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome: A prospective study for more than five years.
BACKGROUND
Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that investigates the clinical characteristics and prognosis of bronchiectasis-COPD overlap syndrome (BCOS). Further, we aimed to explore factors associated with acute exacerbation and death in BCOS, which may be of value in its early diagnosis and intervention.
METHODS
We recruited inpatients with COPD from the second Xiangya Hospital of Central South University in China in August 2016, with follow-up until March 2022. Patients in the BCOS group had to meet the criteria for diagnosing bronchiectasis. We used self-completion questionnaires, clinical records, and self-reported data as primary data collection methods. We used Kaplan-Meier survival analyses and Cox proportional hazard models to assess the risk of severe acute exacerbation and death for BCOS during the follow-up period.
RESULTS
A total of 875 patients were included and followed up. Patients in the BCOS group had more females, fewer smokers, lower discharge COPD assessment test (CAT) scores, lower forced vital capacity (FVC), a higher likelihood of co-occurring active tuberculosis, higher levels of eosinophils and inflammatory markers, and a higher rate of positive sputum cultures for Pseudomonas aeruginosa than patients in the COPD-only group. Patients in the acute exacerbation group (AE+) were found to have lower body mass index (BMI), more frequent acute exacerbations, higher modified Medical Research Council (mMRC) dyspnoea grade on admission, higher inflammatory markers, lower FVC, higher rates of using inhaled bronchodilators, and higher rates of both positive and Pseudomonas aeruginosa positive sputum cultures. Patients in the 'death' group were older, had a lower BMI, had spent longer time in the hospital, had higher mMRC dyspnoea grade and CAT scores upon admission and discharge, had higher levels of inflammatory markers, lower rates of using inhaled bronchodilators, were more likely to have a combination of pulmonary heart disease and obsolete pulmonary tuberculosis, as well as a higher rate of fungus-positive sputum cultures. Both erythrocyte sedimentation rate at baseline and Pseudomonas aeruginosa culture positivity were confirmed as independent predictors of severe acute exacerbation in multivariate analysis during the years of follow-up. Fungus culture positivity baseline blood urea nitrogen, baseline lymphocyte count, comorbidities with obsolete pulmonary tuberculosis and comorbidities with pulmonary heart disease were verified as independent predictors of death in multivariate analysis during the years of follow-up. Kaplan-Meier curves under survival analysis demonstrated no statistically significant difference in mortality between the COPD and the BCOS groups at the full one, two, and three years of follow-up.
CONCLUSIONS
Patients with BCOS present with reduced lung function, increased susceptibility to different complications, elevated blood eosinophils and inflammatory markers, and elevated rates of positive Pseudomonas aeruginosa cultures. These distinctive markers are linked to a greater risk of severe acute exacerbations and mortality.
Topics: Humans; Female; Pulmonary Disease, Chronic Obstructive; Male; Bronchiectasis; Middle Aged; Prospective Studies; Aged; Prognosis; China; Risk Factors; Syndrome; Disease Progression
PubMed: 38940273
DOI: 10.7189/jogh.14.04129 -
JACS Au Jun 2024The first total synthesis of the repeating units of the -antigens of ATCC 27577, O10, and O19 was achieved via a linear glycosylation strategy. This also represents the...
The first total synthesis of the repeating units of the -antigens of ATCC 27577, O10, and O19 was achieved via a linear glycosylation strategy. This also represents the first synthesis of an oligosaccharide containing an α-linked -acetyl-l-galactosaminuronic acid (l-GalNAcA) unit. All of the glycosyl linkages, including three challenging 1,2--glycosidic bonds of amino sugars, were effectively constructed with high to exclusive stereoselectivity, while orthogonal protection tactics were employed to facilitate regioselective glycosylations and the introduction of a variety of functionalities. An acetyl group migration phenomenon was found during the synthesis of the -acylated repeating unit of the ATCC 27577 antigen. All synthetic targets carried an amino functional group in the linker at the reducing end, thus facilitating further regioselective elaboration and biological studies. The synthetic strategy established here should be useful for the preparation of other similar oligosaccharides.
PubMed: 38938791
DOI: 10.1021/jacsau.4c00321 -
Open Veterinary Journal May 2024This research describes the methodology used for the preparation of selenium nanoparticles from and their administration to lambs for lipid profile checking,...
BACKGROUND
This research describes the methodology used for the preparation of selenium nanoparticles from and their administration to lambs for lipid profile checking, administration of selenium nanoparticles as a medication in lambs results in hypolipidemia.
AIMED
The study aimed to investigate the potential of selenium nanoparticles in improving lipid profiles in lambs.
METHODS
Healthy lambs ( = 10) of similar age and weight were selected for the study. The animals were housed in individual pens with free access to water and a standard diet. The lambs were randomly divided into two groups: the control group ( = 5) and the treatment group ( = 5). The control group received a standard diet, while the treatment group received the same diet and oral administrated with selenium nanoparticles at 0.1 mg/kg body weight. The administration was carried out daily for a period of 8 weeks. Blood samples were collected from the jugular vein of each lamb at the beginning of the study (baseline) and at the end of the 2 weeks treatment period. The samples were collected in vacutainer tubes and allowed to clot. Serum was separated by centrifugation at 3,000 rpm for 10 minutes and stored at -80°C for estimation of lipid profile total cholesterol (TC), triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The serum samples were used for the estimation of lipid profile levels using an enzymatic colorimetric method. The absorbance was measured at 540 nm using a spectrophotometer.
RESULTS
The results showed a significant decrease in serum TC, triglyceride, and very-low-density lipoprotein cholesterol levels after selenium nanoparticle supplementation compared to the control group ( < 0.05), the results indicated a significant increase in serum HDL levels after selenium nanoparticle supplementation compared to the control group ( < 0.05). This indicates that selenium nanoparticle supplementation has a beneficial effect on reducing TC levels in lambs.
CONCLUSION
The conclusion section will summarize the findings of the study and highlight the potential of selenium nanoparticles in improving lipid profiles in lambs. The implications of the study for animal nutrition and health will be discussed, along with the need for further research in this area.
Topics: Animals; Selenium; Male; Nanoparticles; Lipids; Sheep; Pseudomonas aeruginosa; Sheep, Domestic
PubMed: 38938439
DOI: 10.5455/OVJ.2024.v14.i5.10 -
Health Technology Assessment... Jun 2024To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund...
BACKGROUND
To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
METHODS
The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
RESULTS
Among isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
CONCLUSION
This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
LIMITATIONS
Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.
FUTURE WORK
Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
STUDY REGISTRATION
No registration of this study was undertaken.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in ; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Cephalosporins; Anti-Bacterial Agents; Quality-Adjusted Life Years; Cost-Benefit Analysis; England; Technology Assessment, Biomedical; Cefiderocol; Gram-Negative Bacterial Infections; State Medicine; Quality of Life
PubMed: 38938145
DOI: 10.3310/YGWR4511 -
Environmental Science & Technology Jun 2024Waterborne pathogens invariably present considerable threats to public health. The quorum sensing (QS) system is instrumental in coordinating bacterial growth and...
Waterborne pathogens invariably present considerable threats to public health. The quorum sensing (QS) system is instrumental in coordinating bacterial growth and metabolisms. However, the responses and regulatory mechanisms of bacteria to various disinfection technologies through quorum sensing are still unclear. This study examines the inactivation effect of chlorination and ozonation on biofilms and planktonic cells of QS signaling-deficient mutants of . Cell counting and viability assessment revealed that the combined disinfection of chlorine and ozone was the most effective for inactivating planktonic within 10 min of exposure. Additionally, microfluidic chip culture demonstrated that the secretion of quinolone signals escalated biofilms' disinfection resistance. Disinfection exposure significantly altered the gene expression of wild-type strains and QS signaling-deficient mutants. Moreover, the QS system triggered multilayered gene expression programs as a responsive protection to disinfectant exposure, including oxidative stress, ribosome synthesis, and the nutrient absorption of bacteria. These insights broaden our understanding of bacterial QS in response to disinfection, promising potential strategies toward efficient disinfection processes.
PubMed: 38937254
DOI: 10.1021/acs.est.3c08305